Project Summary/Abstract Insomnia is a sleep disorder characterized by difficulty falling asleep, staying asleep, or both, despite adequate opportunity for sleep attainment. As a result, people with insomnia may get too little sleep and/or have poor sleep quality. Insomnia is a common and debilitating sleep disorder in persons living with HIV (PLWH), with prevalence estimates ranging from 30-73%. Insomnia is increasingly viewed as a risk factor for the onset and/or worsening of pain symptoms and physical functioning deficits. Insomnia has been found to promote enhanced pain sensitivity (also known as hyperalgesia), which is critical to the etiology of pain in everyday life. This is particularly relevant for PLWH because recent evidence attests to the fact that pain symptoms are quite prevalent in the daily lives of PLWH. Whether insomnia is a risk factor for the experience of pain and poor physical functioning in PLWH is a topic that has received minimal attention to date; therefore, additional research is needed. Inflammatory processes represent an important biologic mechanism linking insomnia to pain and physical function. Insomnia promotes systemic inflammation as well as inflammatory reactivity to physical stressors like pain. Research conducted with non-HIV samples has shown that inflammation can substantially increase sensitivity to painful stimuli in the laboratory setting, as well as exacerbate pain symptoms in everyday life and physical disability. Taken together, insomnia may drive pain and physical function in PLWH through the proliferation of inflammatory mediators. There is currently a need to elucidate mechanisms and mediators of sleep disorders in PLWH, and the consequences and influences of these disturbances on other HIV-related comorbidities. Accordingly, the overall objective of this proposal is to investigate the impact of insomnia on pain, physical function, and inflammation in PLWH. We will accomplish our overall objective by addressing the following specific aims: 1) determine whether insomnia promotes increased experimental pain sensitivity and exaggerated inflammatory reactivity to painful stimuli in PLWH, and 2) determine if fluctuations in insomnia burden over time drive inflammation and pain in everyday life, and physical functioning among PLWH. These aims will be addressed using study methods developed and rigorously refined by our research team, and which have previously yielded promising preliminary results suggesting that insomnia may indeed promote pain and inflammation in PLWH. This approach is innovative because the impact of insomnia on pain and pain-related inflammatory processes has never before been directly examined in PLWH. Furthermore, the incorporation of objective as well as subjective measures of sleep and physical function, experimental pain testing, and a wide array of pro- and anti-inflammatory biomarkers also contributes to the innovation of this proposal. The proposed research will be significant because, if our hypotheses are confirmed, we will identify: 1) insomnia as a major driver of pain and physical functioning in the laboratory and in everyday life among PLWH, and 2) inflammation as an important insomnia-related mediator of pain in PLWH.